Obicetrapib is Safe and Well-Tolerated in HeFH and ASCVD, With Stephen Nicholls, MD

Obicetrapib has a history of being safe and well-tolerated in patients with heterozygous familial hypercholesterolemia (HeFH) and atherosclerotic cardiovascular disease (ASCVD), based on a pooled safety analysis of the BROADWAY and BROOKLYN phase 3 trials.1

These data were presented at the American College of Cardiology (ACC) Scientific Sessions 2026 in New Orleans, Louisiana, by Stephen Nicholls, MD, director of the Monash Velos Accelerator, program director of MonashHeart, Intensive Care and Victorian Heart Hospital, and director of the Monash Victorian Heart Institute at Monash Health.

“We saw less new onset diabetes, which we’ve seen with other CETP inhibitors, and we’ve also seen some potential favorable effects in slowing the reduction of eGFR,” Nicholls told HCPLive in an exclusive interview. “I think we need to understand more about potential mechanisms, but most importantly, this reassures me about safety and tolerability, and if we can combine that with better lipid effects and ultimately a reduction in cardiovascular risks, that would be great for patients.”

BROADWAY was a multinational, placebo-controlled, double-blind phase 3 trial including patients with either HeFH or established ASCVD. Additional criteria included being on maximally tolerated lipid-modifying therapy, a fasting serum LDL-C ≥55 to <100 mg/dL or non-DL-C ≥85 mg/dL to <130 mg/dL, and an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73m2 at screening, among others. Patients were excluded if they had NYHA class III or IV heart failure, left ventricular ejection fraction <30%, or major adverse cardiovascular events within 3 months of screening, among other criteria.2

A total of 2530 patients were included in the trial and were randomly assigned to either obicetrapib 10 mg or placebo daily for 365 days. Over the course of the study, eGFR decreased significantly more among patients receiving obicetrapib compared to placebo. LDL-C also changed by a comparatively larger amount in the obicetrapib arm (-29.9%) versus placebo (+2.7%).3

The BROOKLYN trial, meanwhile, specifically investigated patients with HeFH who were on maximally tolerated lipid-modifying therapy. Patients were excluded if they had NYHA class II or IV heart failure, last known left ventricular ejection fraction <30%, or had been hospitalized for heart failure within 5 years of screening, among other criteria.4

The BROOKYLN investigators enrolled 354 patients and randomly assigned them in a 2:1 ratio to either obicetrapib 10 mg or placebo daily for 365 days. During this time, patients exhibited a placebo-adjusted LDL-C change of -36.3%. Secondary endpoints included changes in apolipoprotein B and non-HDL-C, which decreased by 24.4% and 34.5%, respectively.5

For the present safety analysis, Nicholls and colleagues pooled data from both trials for a total of 2880 patients. The frequency of overall treatment-emergent adverse events was similar between obicetrapib and placebo groups (60.2% vs 62%). Adverse events leading to discontinuation were 4.1% and 5.3%, respectively. Among predicted events, dizziness, headache, hypertension, and myalgia were infrequent, while new onset diabetes mellitus, worsening glycemic control, and eGFR decline occurred less frequently with obicetrapib. Additionally, macular degeneration was rare and occurred in only 1 obicetrapib recipient.1

“We know that many patients don’t get to goal, and every time we update our guidelines, they tell us that high-risk patients should go lower and lower,” Nicholls said. “But every time we lower the target, we’re going to leave more and more people behind. So, we need effective therapies that we can add to statins. Obicetrapib has the potential to be that therapy.”

Editors’ Note: Nicholls reports disclosures with AstraZeneca, NewAmsterdam Pharma, Amgen, Omthera, Merck, Boehringer Ingelheim, and others.

References

1. Nelson A, Kastelein J, Hsieh A, et al. Safety of Obicetrapib: An Integrated Pooled Phase III Safety Analysis. Abstract presented at the American College of Cardiology Scientific Sessions 2026, New Orleans, LA. March 28-30, 2026.

2. NewAmsterdam Pharma. Randomized Study to Evaluate the Effect of Obicetrapib on Top of Maximum Tolerated Lipid-Modifying Therapies (BROADWAY). ClinicalTrials.gov Identifier: NCT05142722. Updated September 19, 2025. Accessed April 2, 2026. https://clinicaltrials.gov/study/NCT05142722

3. Nicholls SJ, Nelson AJ, Ditmarsch M, et al. Safety and efficacy of Obicetrapib in patients at high cardiovascular risk. NEJM. 2025;393(1):51-61. doi:10.1056/nejmoa2415820

4. NewAmsterdam Pharma. Evaluate the Effect of Obicetrapib in Patients With HeFH on Top of Maximum Tolerated Lipid-Modifying Therapies (BROOKLYN). ClinicalTrials.gov Identifier: NCT05425745. Updated June 11, 2025. Accessed April 2, 2026. https://clinicaltrials.gov/study/NCT05425745

5. Nicholls, S.J., Nelson, A.J., Ditmarsch, M. et al. Obicetrapib in patients with heterozygous familial hypercholesterolemia: the BROOKLYN randomized clinical trial. Nat Med 32, 1052–1060 (2026). https://doi.org/10.1038/s41591-025-04179-4